Abstract: The STING pathway is an essential innate immune pathway that is activated when double stranded DNA is detected in the cytosol. This occurs during viral infection and tumorigenesis and activation of the pathway elicits strong anti-viral and anti-cancer immunity. However, double stranded DNA is also misplaced in the cytosol during trauma, radiation, autoimmune syndromes, and aging. In these cases, STING activation exacerbates the unwanted immunity against healthy tissues. Our lab dissects activation, inhibition, and regulatory mechanisms of the STING pathway from the atomic level to tissue level. In parallel, we develop tool compounds and drug leads to toggle the activation level of the pathway in a cell type and disease specific manner.